Updates from ASPIRE and ENDEAVOR: Multicenter phase III studies of carfilzomib for relapsed/refractory multiple myeloma

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Published: 2 Mar 2017
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Dr David Siegel - John Theurer Cancer Center, Hackensack, USA

Dr Siegel talks to ecancer at the 16th International Myeloma Workshop about the ASPIRE trial, looking at carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.

He also discusses the ENDEAVOUR trial looking at carfilzomib in combination with low-dose dexamethasone (Kd), versus bortezomib with low-dose dexamethasone (Vd) in patients whose multiple myeloma has relapsed after at least one, but not more than three prior therapeutic regimens. 

Since presentation at ASH 2015 the data from both trials has matured. Consistent with the primary analyses, the results show that incorporation of carfilzomib into treatment regimens in patients with relapsed or refractory multiple myeloma results in clinically meaningful improvements in progression free survival and a favourable benefit–risk profile.

Read more here.

Carfilzomib is also being trialled combination therapies for for newly diagnosed myeloma, as discussed by Dr Boccia here.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

Most of the myeloma community is aware of both of these clinical trials. This is a combined dataset that has slightly more mature data. One of the primary issues has been about toxicity of carfilzomib and both of these studies continue to show that patients on the carfilzomib arm of these studies come off of therapy less frequently on the carfilzomib arm because of toxicity related issues than on the control arm. So that’s very interesting given that patients were on the carfilzomib based therapies for about 50% longer than they were on the alternatives so the fact that this data continues to be the case is one of the most important things because perhaps the biggest barrier to utilisation of carfilzomib has been largely unfounded concerns about toxicity. That is perhaps the most important observation.

In terms of efficacy it continues to show a significantly superior efficacy for the carfilzomib containing arms although, just to be clear, one of these trials is lenalidomide and dexamethasone versus carfilzomib lenalidomide and dexamethasone, that’s the ASPIRE trial, and one is higher dose carfilzomib and dexamethasone versus bortezomib and dexamethasone. In both of those clinical trials the efficacy signal was enormous: the carfilzomib arm of the ASPIRE trial is probably the single best arm in any randomised clinical trial to date. The high dose carfilzomib arm of the carfilzomib bortezomib, to a great extent, lays to rest the issue of which is the most efficacious proteasome inhibitor.

What toxicities are you seeing?

The biggest concerns are cardiac or cardiopulmonary kinds of toxicities. So the number one kind of issue with carfilzomib is shortness of breath and that is the concern. While it certainly is a real toxicity, it shouldn’t be a barrier to utilisation of carfilzomib, at least in my opinion.

How mature is this data?

The original presentations were from ASH two ASHs ago so with that much more follow-up. The combined dataset and the toxicity issues are probably the most important aspect of this.

Could we potentially see a change in standard of care?

To some extent we have seen that already; there are significant datasets. Andrzej Jakubowiak from the University of Chicago certainly deserves much of the credit for examining the upfront utilisation of carfilzomib in combination with lenalidomide and dexamethasone and in our efforts to cure myeloma this is going to be the centrepiece of that. Whether we see additional drugs, clearly there’s some excitement about carfilzomib lenalidomide dexamethasone plus daratumumab as an initial intervention for patients with multiple myeloma, is that going to be the thing that gets us over the hump, at least in a subset of patients with multiple myeloma so that we can really see biological cures? That’s something that the myeloma community is very excited about.